Image-guided focused ultrasound ablation of breast cancer: current status, challenges, and future directions.

Image-guided focussed ultrasound (FUS) ablation is a non-invasive procedure that has been used for treatment of benign or malignant breast tumours. Image-guidance during ablation is achieved either by using real-time ultrasound (US) or magnetic resonance imaging (MRI). The past decade phase I studies have proven MRI-guided and US-guided FUS ablation of breast cancer to be technically feasible and safe. We provide an overview of studies assessing the efficacy of FUS for breast tumour ablation as measured by percentages of complete tumour necrosis. Successful ablation ranged from 20% to 100%, depending on FUS system type, imaging technique, ablation protocol, and patient selection. Specific issues related to FUS ablation of breast cancer, such as increased treatment time for larger tumours, size of ablation margins, methods used for margin assessment and residual tumour detection after FUS ablation, and impact of FUS ablation on sentinel node procedure are presented. Finally, potential future applications of FUS for breast cancer treatment such as FUS-induced anti-tumour immune response, FUS-mediated gene transfer, and enhanced drug delivery are discussed. Currently, breast-conserving surgery remains the gold standard for breast cancer treatment.

Contrast-enhanced 3.0-T breast MRI for characterization of breast lesions: increased specificity by using vascular maps.

PURPOSE: To assess the diagnostic accuracy of contrast-enhanced 3.0-T breast magnetic resonance imaging (MRI) for differentiating benign from malignant breast masses and subsequently to test if specificity could be further improved by scoring of the overall ipsilateral breast vascularity. MATERIALS AND METHODS: Fifty-four patients were prospectively enrolled in the study and underwent contrast-enhanced 3.0-T breast MRI. MR images were evaluated and classified according to the MRI BI-RADS lexicon criteria. Lesion size, number of lesions, and localization in the breast were systematically assessed. Maximum intensity projections (MIPS) were obtained by using high-resolution contrast-enhanced (0.1 mmol/kg gadobutrol) fat-saturated T1-weighted images. Breast vascularization was scored according to the methods from Sardanelli et al. by measuring the number, diameter, and length of the vessels on the MIPS. The score ranged from 0 (indicating absent or low breast vascularity) to 3 (indicating high breast vascularity). RESULTS: Final analysis of 56 lesions revealed 25 (45%) malignant lesions and 31 (55%) benign lesions. Correlation with the MRI BI-RADS classification revealed cancer in none (0%) of the BI-RADS II lesions, in 1 (12%) of the BI-RADS III lesions, in 5 (83%) of the BI-RADS IV lesions, and in 19 (100%) of the BI-RADS V lesions. Based on morphologic and kinetic data analysis, the sensitivity and specificity of 3.0-T breast MRI was 100% (25/25) and 74% (23/31), respectively. After adjustment for the breast vascularity score, specificity significantly (p = 0.048) increased to 87% (27/31) without affecting sensitivity. CONCLUSION: Diagnostic accuracy of contrast-enhanced 3.0-T breast MRI increased significantly when the vascularity score was added to the standard morphologic and kinetic data analysis, resulting in a specificity of 87% without affecting sensitivity, which remained 100%.

A genome-wide survey of RAS transformation targets.

An important aspect of multi-step tumorigenesis is the mutational activation of genes of the RAS family, particularly in sporadic cancers of the pancreas, colon, lung and myeloid system. RAS genes encode small GTP-binding proteins that affect gene expression in a global way by acting as major switches in signal transduction processes, coupling extracellular signals with transcription factors. Oncogenic forms of RAS are locked in their active state and transduce signals essential for transformation, angiogenesis, invasion and metastasis via downstream pathways involving the RAF/MEK/ERK cascade of cytoplasmic kinases, the small GTP-binding proteins RAC and RHO, phosphatidylinositol 3-kinase and others. We have used subtractive suppression hybridization (SSH), a PCR-based cDNA subtraction technique, to contrast differential gene expression profiles in immortalized, non-tumorigenic rat embryo fibroblasts and in HRAS- transformed cells. Sequence and expression analysis of more than 1,200 subtracted cDNA fragments revealed transcriptional stimulation or repression of 104 ESTs, 45 novel sequences and 244 known genes in HRAS- transformed cells compared with normal cells. Furthermore, we identified common and distinct targets in cells transformed by mutant HRAS, KRAS and NRAS, as well as 61 putative target genes controlled by the RAF/MEK/ERK pathway in reverted cells treated with the MEK-specific inhibitor PD 98059.